Aim:Exploring the relationship between two polymorphisms (MMP-1-755 T/G [rs498186] and MMP-3 A/C [rs632478]) and disc degeneration. Material and Methods:We performed a case-control study on 130 cases with intervertebral disc degeneration confirmed by Magnetic Resonance Imaging (MRI) and 210 healthy individuals. Schneiderman criterion was used to determine the severity of the disc degeneration. Blood samples were collected from the participants. The genotyping was performed by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Odds ratios and 95%CIs were determined as measures of the strength of association between genotypes and disc degeneration. Results:The most frequent intervertebral disc degeneration was observed in age range of 31-40 years (43.2%). A significant association was found between the MMP-3 polymorphism and disc degeneration (P<0.001). The homozygote CC was associated with an increased risk of disc degeneration compared with AA genotype (OR=5.25; 95%CI=2.82-9.77, P<0.001). We did not find any significant association of the MMP-1 polymorphism with disc degeneration (P=0.95).Conclusion:The MMP-3 [rs632478] polymorphism may contribute to the susceptibility of disc degeneration. To confirm our findings, additional well-designed studies in diverse ethnic populations are required.